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Biomedical subjects

A Graffi

Publications and source records attributed to A Graffi.

At least 55 records · Page 3Linked to original sources
PubMed1970

Preferential alkylation of mitochondrial deoxyribonucleic acid by N-methyl-N-nitrosourea.

The reaction of the carcinogen N-methyl-N-nitrosourea with mitochondrial DNA from various rat tissues was examined in vivo and in vitro. After incubation of isolated mitochondria or cell nuclei with N[(14)C]-methyl-N-nitrosourea in vitro and subsequent isolation and purification of the DNA the specific radioactivity of the mitochondrial DNA was 3-7 times that of the nuclear DNA. The incorporation of (14)C into embryonic mitochondrial DNA in vitro was about twice that into the liver mitochondrial DNA. Identical incorporation rates, however, were found for the reaction of isolated mitochondrial DNA or nuclear DNA respectively with N[(14)C]-methyl-N-nitrosourea. After intraperitoneal injection of 43.3-58.5mg of N[(14)C]-methyl-N-nitrosourea/kg body wt. to adult rats the labelling of the mitochondrial DNA was on average 5 times that of the nuclear DNA. A smaller specific labelling was observed for the ribosomal RNA, transfer RNA, and mitochondrial RNA as well as for the mitochondrial protein as compared with the mitochondrial DNA. After hydrolysis of the alkylated nucleic acids with hydrochloric acid, fractionation was carried out on Dowex 50 cation-exchange columns. In most experiments 70-80% of the input (14)C radioactivity was eluted in the 7-methylguanine fraction. The preferential alkylation of the mitochondrial DNA by N-methyl-N-nitrosourea in situ is discussed in connexion with the cytoplasmic-mutation hypothesis of carcinogenesis.

Alkylation↗
PubMed1969

Induction of transmissible lymphomas in Syrian hamsters by application of DNA from viral hamster papovavirus-induced tumors and by cell-free filtrates from human tumors.

DNA isolated from skin epitheliomas containing papovavirus induced lymphomas within four to eight weeks in 40 to 50 per cent of newborn Syrian hamsters injected. This DNA effect was eliminated by DNase but not by RNase and was not induced by DNA preparations of transplanted epitheliomas or the induced lymphomas. Lymphomas were similarly induced by cellfree filtrates from certain human tumors such as gastric carcinomas and ovarian tumors. Little or no lymphoma effects were observed following injections with filtrates derived from normal human or animal tissues or human blood. The lymphomas induced by DNA and human tumors were transmissible by cell-free filtrates to newborn Syrian hamsters; however, successful serial passage, like the primary lymphomas induced by the DNA preparations, depended upon the use of a newborn hamster from a special breeding colony of hamsters.

Animals↗